The opportunistic fungal pathogen Aspergillus fumigatus is the causative agent of more than 90% of all Invasive Aspergillosis (IA) infections diagnosed in immunosuppressed patients. Exposure to A. fumigatus can also lead to the development of allergic asthma and Allergic Bronchopulmonary Aspergillosis (ABPA) in patients with atopic asthma or Cystic Fibrosis. Fungus-specific CD4 T cell responses are important in defense against invasive disease and mediate the development of allergic responses. Thus, understanding the factors that control the expansion and formation of fungus-specific memory CD4 T cells will lay the foundation for the future development of novel immune-based therapeutic strategies to enhance or inhibit fungus-specific immunity. In this proposal, the applicant will examine the contributions of regulatory T cells (Tregs) and T cell-intrinsic inhibitry receptors (PD-1 and CTLA-4) in controlling fungus-specific CD4 T cell responses. Moreover, the proposed studies will determine the mechanism of action of inhibitory receptors and Tregs and how they impact fungus-driven allergic airway disease progression. The applicant will be supported by a comprehensive training plan to promote her career development as an independent scientist and to help her attain a PhD degree. The long-term goal of the applicant is to become a successful, well- funded, independent researcher. As a woman of Hispanic descent the applicant is committed to contributing to the future development of research programs to address health disparities and diversity in biomedical science's workforce.

Public Health Relevance

The opportunistic fungal pathogen Aspergillus fumigatus is the most common causative agent of invasive aspergillosis and can also trigger the development of allergic asthma responses. Immune responses to this fungus are central in the pathogenesis of fungal allergic asthma and in the prevention of invasive fungal disease. The studies proposed in this application will elucidate the specific contributions of immune regulatory mechanisms that promote the proper eradication of A. fumigatus while preventing excessive tissue damage to the host. The characterization of relevant immune regulatory mechanisms will facilitate the development of novel immune based therapeutic interventions for the treatment of invasive fungal disease and allergic asthma.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F07-K (20))
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Adger-Johnson, Diane S
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University of Medicine & Dentistry of NJ
Schools of Medicine
United States
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Gupta, Anukriti; Espinosa, Vanessa; Galusha, Lindsey E et al. (2015) Expression and targeting of lymphocyte function-associated antigen 1 (LFA-1) on white blood cells for treatment of allergic asthma. J Leukoc Biol 97:439-46
Espinosa, Vanessa; Jhingran, Anupam; Dutta, Orchi et al. (2014) Inflammatory monocytes orchestrate innate antifungal immunity in the lung. PLoS Pathog 10:e1003940